Perioperative myocardial ischemia and cardiovascular dysfunction are among the most serious anesthetic complications. Changes in regional contractility, perfusability and O2 supply-demand balance with the administration of anesthesia are more closely related to development of myocardial ischemia and/or infarction than left ventricular (LV) global changes. Most investigations of anesthetic effects on the ischemic heart have focused on global changes, assuming LV is a uniformly-functioning unit, thus providing insufficient or misleading information for the clinician. Regional intramyocardial tissue pressure (IMP) is an important parameter which is closely related to regional wall tension and contractility, and, therefore regional myocardial O2 consumption. IMP is also a major determinant for regional myocardial perfusion. Measuring IMP simultaneously with regional segmental length, myocardial blood flow, and intramyocardial EKG, we propose to investigate the effects of anesthetics on regional mechanics, perfusability, and oxygen supply- demand balance of the following areas of LV of chronically instrumented dogs: 1. Endocardium vs. epicardium in normal LV; 2. Regions supplied by a critically narrowed artery vs. normal areas; 3. Regions rendered briefly ischemic and subsequently reperfused in comparison to normally-perfused areas. Anesthetic effects on regional myocardium will then be contrasted with simultaneous changes in global function. Our studies will result in a comprehensive picture of anesthetic effects on regional physiological and metabolic parameters and their contributions to the development or prevention of myocardial ischemia. They will also extend our understanding of modulation by anesthetics of the processes of ischemia, reperfusion and recovery. In the second phase, years 4 and 5, we will apply this experimental design to study inotropic drugs commonly used to resuscitate myocardium after ischemia and stunning during surgical anesthesia. Thus, we will evaluate the effects of these drugs on regional myocardial function, regional oxygen supply-demand balance, and compare their actions on regional parameters between ischemic/reperfused areas and normally perfused areas, as well as with global function. These experiments will provide the basis for future work in several areas, including 1. interactions between anesthetics, inotropic drugs, and vasodilators used in surgical anesthesia, 2. modification by various drugs and anesthetics of vascular reactivity of coronary arteries after ischemia and reperfusion, and 3. clinical application of IMP for assessing regional myocardial function and O2 balance under anesthesia in patients with ischemic heart disease.